The delta opioid receptor is possessed of many pharmacological actions as described above. Compounds having high selectively for this receptor promise adoption as analgesics, immunosuppressants, immunopotentiating agents, and antihypertensive agents. Except for peptide type compounds, no ligand of high selectivity for the delta receptor has been discovered until recent years. The peptide type compounds have not easily permitted their own development as the medicines mentioned above because they have the fault that they encounter difficulty in passing the blood-brain barrier with yield easily to in vivo decomposition with peptidase. Thus, agonists and antagonists possessed of high selectivity for the delta receptor are in demand. Recently, Portoghese et al have discovered an antagonist, NTI, possessed of high selectivity for the delta-opioid receptor (P. S. Portoghese et al., J. Med. Chem., Vol. 31, No. 2, 1988). This NTI is an alkaloid and, unlike peptides, is free from the problem of passage through the blood-brain barrier and the problem of decomposition with a peptidase. The NTI, however, is problematic in respect that the cost of its production is high because it is synthesized from naltrexone as a raw material and the naltrexone is difficult to procure because it is synthesized from thebaine which is a narcotic. As regards delta receptor agonists, peptides such as DADLE and DPDPE have been known in the art. Alkaloids of high selectivity remain to be developed.
An object of this invention is to provide a ligand (agonist and antagonist) which has a high affinity and selectivity for the delta receptor promising to manifest the aforementioned pharmacological actions, attains synthesis of its own through a route not using a narcotic as a raw material, passes through the blood-brain barrier, enjoys high stability in resisting a peptidase, and is not excessively expensive.